A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia.

Abstract

We have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia type 2 (MacTel 2), which is a retinal disease of unknown cause. Genetic analyses showed that the BN-J phenotype results from an autosomal recessive indel novel mutation in the Crb1 gene, causing dislocalization of the protein from the retinal Müller glia (RMG)/photoreceptor cell junction. The transcriptomic analyses of primary RMG cultures allowed identification of the dysregulated pathways in BN-J rats compared with wild-type BN rats. Among those pathways, TGF-β and Kit Receptor Signaling, MAPK Cascade, Growth Factors and Inflammatory Pathways, G-Protein Signaling Pathways, Regulation of Actin Cytoskeleton, and Cardiovascular Signaling were found. Potential molecular targets linking RMG/photoreceptor interaction with the development of retinal telangiectasia are identified. This model can help us to better understand the physiopathologic mechanisms of MacTel 2 and other retinal diseases associated with telangiectasia.

• Authors: Min Zhao, Charlotte Andrieu-Soler, Laura Kowalczuk, María Paz Cortés, Marianne Berdugo, Marilyn Dernigoghossian, Francisco Halili, Jean-Claude Jeanny, Brigitte Goldenberg, Michèle Savoldelli, Mohamed El Sanharawi, Marie-Christine Naud, Wilfred van Ijcken, Rosanna Pescini-Gobert, Danielle Martinet, Alejandro Maass, Jan Wijnholds, Patricia Crisanti, Carlo Rivolta, Francine Behar-Cohen
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 35 Issue 15 Pg. 6093-106 (Apr 15 2015) ISSN: 1529-2401 [Electronic] United States
• PMID: 25878282 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the authors 0270-6474/15/356093-14$15.00/0.

Chemical References

• Eye Proteins
• Glial Fibrillary Acidic Protein
• Platelet Endothelial Cell Adhesion Molecule-1

Topics

• Age Factors
• Animals
• Animals, Newborn
• Cells, Cultured
• Disease Models, Animal
• Electroretinography
• Ependymoglial Cells (metabolism, pathology, ultrastructure)
• Eye Proteins (genetics, metabolism)
• Fluorescein Angiography
• Glial Fibrillary Acidic Protein (metabolism)
• Mutation (genetics)
• Neurons (pathology, ultrastructure)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Rats
• Rats, Mutant Strains
• Retinal Degeneration (etiology, genetics, pathology)
• Retinal Vessels (pathology, ultrastructure)
• Signal Transduction (physiology)
• Telangiectasis (complications, genetics)
• Visual Pathways (pathology, ultrastructure)